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Evidence for the involvement of distinct signal transduction pathways in
the regulation of constitutive and interferon gamma-dependent gene
expression of NADPH oxidase components (gp91-phox, p47-phox, and p22- phox)
and high-affinity receptor for IgG (Fc gamma R-I) in human
polymorphonuclear leukocytes
MA Amezaga, F Bazzoni, C Sorio, F Rossi and MA Cassatella
Institute of General Pathology, University of Verona, Italy.
We recently showed that mRNA levels coding the high-affinity Fc gamma
receptor for IgG (Fc gamma R-I, CD64) and two of the components of the
phagocytic superoxide anion-generating system--the heavy-chain subunit of
cytochrome b558 (gp91-phox) and the 47-Kd cytosolic factor (p47- phox)--are
modulated by interferon gamma (IFN-gamma). In this study, we examined
whether dexamethasone (DEX) affects gp91-phox and p47-phox mRNA expression
of human polymorphonuclear leukocytes (PMN), treated or not with IFN-gamma.
We also investigated whether staurosporine, a general inhibitor of protein
kinases, influences gp91-phox, p47-phox, and Fc gamma R-I gene expression
in PMN treated with or without IFN- gamma. We found that (1) gp91-phox mRNA
steady-state levels, expressed in control or IFN-gamma-treated PMN, were
significantly inhibited, in a dose-dependent fashion, by both DEX and
staurosporine; (2) p47-phox mRNA steady-state levels, expressed in control
or IFN-gamma-treated PMN, were not influenced by DEX, but were markedly
depressed by staurosporine; (3) no changes of spectrophotometric cytochrome
b558 were found in PMN treated for up to 20 hours with the inhibitors,
regardless of the presence of IFN-gamma; (4) both DEX and staurosporine
dose-dependently inhibited IFN-gamma-induced Fc gamma R-I mRNA and protein
expression; and (5) stability of gp91-phox and Fc gamma R-I messages in
IFN-gamma-treated PMN was not altered by the presence of DEX. Our results
demonstrate that gp91-phox, p47-phox, and Fc gamma R-I gene expression of
PMN is governed by specific and independent biochemical pathways. Moreover,
IFN-gamma activates different signal transduction pathways to modulate mRNA
expression of gp91-phox, p47- phox, and Fc gamma R-I.
Volume 79,
Issue 3,
pp. 735-744,
02/01/1992
Copyright © 1992 by The American Society of Hematology
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